Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1 Journal Article
| Authors: | Ough, M.; Lewis, A.; Bey, E. A.; Gao, J.; Ritchie, J. M.; Bornmann, W.; Boothman, D. A.; Oberley, L. W.; Cullen, J. J. |
| Article Title: | Efficacy of β-lapachone in pancreatic cancer treatment: Exploiting the novel, therapeutic target NQO1 |
| Abstract: | NAD(P)H:quinone oxidoreductase (NQO1) is elevated in human pancreatic cancers. We hypothesized that β-lapachone, a novel 1,2-naphthoquinone with potential antitumor activity in cancer cells expressing elevated levels of NQO1, would induce cytotoxicity in pancreatic cancer cells, wherein this two-electron reductase was recently found elevated, β-lapachone decreased clonogenic cell survival, metabolic cell viability, and anchorage-independent growth in soft agar. The cytotoxic in vitro effects of β-lapachone were inhibited with coadministration of dicumarol, a specific inhibitor of NQO1. In preestablished human pancreatic tumor xenografts in nude mice, β-lapachone demonstrated greater tumor growth inhibition when given intratumorally compared to when complexed with cyclodextrin to increase its bioavailability. Due to the poor prognosis of patients with pancreatic cancer and the limited effectiveness of surgery, chemotherapy, and radiation therapy, treatment regimens based on sound, tumor-specific rationales are desperately need for this disease. ©2005 Landes Bioscience. |
| Keywords: | cancer chemotherapy; controlled study; aged; cancer surgery; unclassified drug; human cell; drug efficacy; nonhuman; drug targeting; cancer radiotherapy; pancreas cancer; mouse; cell viability; cell survival; drug inhibition; enzyme inhibition; cell growth; tumor volume; animal experiment; animal model; antineoplastic activity; cytotoxicity; in vitro study; tumor xenograft; enzyme inhibitor; drug antagonism; cancer cell; reactive oxygen species; single drug dose; quinones; drug bioavailability; pancreatic cancer; cell protection; clonogenesis; drug solubility; menadione; beta lapachone; agar; cyclodextrins; cyclodextrin; dicoumarol; b-lapachone; nad(p)h:quinone oxidoreductase; 1,2 naphthoquinone; nadph:quinone oxidoreductase; reduced nicotinamide adenine dinucleotide phosphate dehydrogenase |
| Journal Title: | Cancer Biology and Therapy |
| Volume: | 4 |
| Issue: | 1 |
| ISSN: | 1538-4047 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2005-01-01 |
| Start Page: | 95 |
| End Page: | 102 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15662131 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 37" - "Export Date: 24 October 2012" - "Source: Scopus" |
